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- W1995734577 abstract "ABSTRACT Serine protease inhibitor elafin (E) and its precursor, trappin-2 (Tr), have been associated with mucosal resistance to HIV-1 infection. We recently showed that Tr/E are among principal anti-HIV-1 molecules in cervicovaginal lavage (CVL) fluid, that E is ∼130 times more potent than Tr against HIV-1, and that Tr/E inhibited HIV-1 attachment and transcytosis across human genital epithelial cells (ECs). Since herpes simplex virus 2 (HSV-2) is a major sexually transmitted infection and risk factor for HIV-1 infection and transmission, we assessed Tr/E contribution to defense against HSV-2. Our in vitro studies demonstrated that pretreatment of endometrial (HEC-1A) and endocervical (End1/E6E7) ECs with human Tr-expressing adenovirus (Ad/Tr) or recombinant Tr/E proteins before or after HSV-2 infection resulted in significantly reduced virus titers compared to those of controls. Interestingly, E was ∼7 times more potent against HSV-2 infection than Tr. Conversely, knockdown of endogenous Tr/E by small interfering RNA (siRNA) significantly increased HSV-2 replication in genital ECs. Recombinant Tr and E reduced viral attachment to genital ECs by acting indirectly on cells. Further, lower viral replication was associated with reduced secretion of proinflammatory interleukin 8 (IL-8) and tumor necrosis factor alpha (TNF-α) and decreased NF-κB nuclear translocation. Additionally, protected Ad/Tr-treated ECs demonstrated enhanced interferon regulatory factor 3 (IRF3) nuclear translocation and increased antiviral IFN-β in response to HSV-2. Lastly, in vivo studies of intravaginal HSV-2 infection in Tr-transgenic mice (Etg) showed that despite similar virus replication in the genital tract, Etg mice had reduced viral load and TNF-α in the central nervous system compared to controls. Collectively, this is the first experimental evidence highlighting anti-HSV-2 activity of Tr/E in female genital mucosa." @default.
- W1995734577 created "2016-06-24" @default.
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- W1995734577 creator A5061445934 @default.
- W1995734577 creator A5069146367 @default.
- W1995734577 creator A5076958594 @default.
- W1995734577 date "2013-07-01" @default.
- W1995734577 modified "2023-10-14" @default.
- W1995734577 title "Antiviral Activity of Trappin-2 and Elafin <i>In Vitro</i> and <i>In Vivo</i> against Genital Herpes" @default.
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- W1995734577 doi "https://doi.org/10.1128/jvi.02243-12" @default.
- W1995734577 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3700282" @default.
- W1995734577 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23637403" @default.
- W1995734577 hasPublicationYear "2013" @default.
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